Odor information is encoded by selective activation of olfactory receptors and mapped topographically to glomeruli in the olfactory bulb. Our broad, long term objective is to understand dendritic and synaptic signaling mechanisms in the bulb that transform this mapped input into odor-encoding spike patterns in output neurons, mitral cells and tufted cells. This application is in response to NOT-OD-09-058: "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". We will expand the scope of the specific aims of the parent award. The approved aims investigate signaling in tufted cells, focusing on synchronization, granule cell synaptic connections and neuromodulation by cholecystokinin. This Revision expands our studies to cover neuromodulation of synaptic transmission between mitral and granule cells of the olfactory bulb by nitric oxide (NO). Our new Specific Aim will test the hypothesis that NO signaling in the olfactory bulb activates soluble guanylyl cyclase (sGC) in a subset of granule cells, leading to upregulation of granule cell calcium which drives increased GABAergic inhibition of mitral cells. The new aim augments and synergizes with aims of the parent grant. Our experimental approaches include electrophysiology and optical recording or stimulation of neurons in slice preparations in a mouse model. PUBLIC HEALTH RELEVANCE: This work will elucidate the neurophysiological mechanisms of NO signaling in the olfactory bulb. These mechanisms not been studied at the cellular level, in spite of anatomical and behavioral evidence implicating NO in olfactory function, including odor memory formation. Our research will offer new insights into regulation of neural activity underlying sensory function in the brain. It has potential relevance for understanding neurodegenerative disorders such as Alzheimers disease which cause olfactory impairment and memory loss. NO signaling is implicated in inflammatory diseases,cancer, diabetes.anxiety, addiction, depression and schizophrenia. This CRA will provided much needed support for the Monell Center, the nation's only non-profit basic research center devoted to chemical senses: taste, smell, and chemesthesis. Monell's discoveries extend across a broad range of disciplines and add value to the local and national economy. Monell currently employs 150 staff members and in recent years has generated close to $16M annually in regional economic activity. The Center's training programs produce highly-skilled research scientists for the future. The current proposal will help retain two positions at Monell, including a highly trained research associate scientist, thus directly contributing to economic stimulus and recovery.